Antibiotics such as anti-bacterial agents and anti-fungal agents are traditionally known to be effective for preventing or treating various infectious diseases and are widely used for clinical applications today. These antibiotics can be obtained by the extraction of products from bacteria or fungi or by chemical synthesis. However, when antibiotics of the same line are used repeatedly for a long period, the target bacteria may acquire resistance against the antibiotics and the effect of the antibiotics may not be developed anymore. This emergence of so-called resistant bacteria has become a serious social problem.
Thus, alternative approaches for protecting hosts via routes different from those of antibiotics have been considered. One representative example involves the potentiation of the immune functions of a host to protect the host from microbial infections. Examples of drugs useful for this approach include immunopotentiators/infection defense medicines and medicines for treating infections comprising riboflavin, which is known widely as vitamin B2, or riboflavin derivatives such as riboflavin mononucleotides, and flavinadenine dinucleotides as described in the gazette of Japanese Kokai Publication Hei-5-201864 or corresponding U.S. Pat. Nos. 5,814,632 and 5,945,420.
Ascorbic acid, known as vitamin C, is also known to have the similar effect. It is described in JP-A 9-301861 that ascorbic acid derivatives are effective on bacterial shocks.
Furthermore, the gazette of Japanese Kokai Publication 2000-297046 discloses that an extract from sweet potato has an effect of stimulating immune of a living body and of preventing infections.
A systemic inflammatory reaction against infections, namely sepsis; i.e., systemic inflammatory response syndrome (SIRS), is a state where a microorganism such as a bacterium or a fungus developed in an infected host is proliferated in a large quantity in the living body and the cells of the microorganism or a metabolite thereof is transferred to the blood and circulated through the body. As this state is progresses, an exotoxin excreted from the microorganism cells or an endotoxin released upon the disruption of the microorganism cells, or a component constituting the microorganism cells is transferred to organs of the host. In the initial stage, fever, malaise and chill occur. As the condition progresses, multiple organ failure develops and symptoms such as impaired consciousness, dyspnea or decreased blood pressure occur, causing a state of shock often followed by death.
Consequently, potent antibiotics are administered to kill microorganisms in the infected host in the initial stage of sepsis, and systemic management such as reinfusion or artificial respiration is applied and simultaneously hemodialysis, plasma exchange or administration of a drug (catecholamine) is performed in the advanced stages. However, the efficacy of these approaches is not always satisfactory.
Recently, medicines for preventing or treating toxin shocks comprising vitamin B2 have been reported in the gazette of Japanese Kokai Publication Hei-10-29941. In addition, the gazette of Japanese Kokai Publication 2000-178246 discloses cycloalkene derivatives for use in the treatment of septic shock; the gazette of Japanese Kokai Publication 2000-80046 discloses medicines for preventing or treating syndromes that develop in the exacerbated state of sepsis; and the gazette of Japanese Kokai Publication 2000-302768 discloses hydrazone derivatives for use in the treatment of endotoxin shock. Furthermore, the gazettes of Japanese Kokai Publication Hei-5-201864 and of Japanese Kokai Publication Hei-10-29941 disclose medicines for immunostimulation and infection-protection and -treatment comprising riboflavin and/or a riboflavin derivative as active ingredient and medicines for preventing or treating toxin shocks, respectively. However, no description about reduced riboflavin is found in these patent publications.
Turning to infections from the malaria protozoa, Japanese patent publication No. Hei-6-506212 discloses that riboflavin is effective for the prevention and treatment of malarian diseases. Furthermore, Antimicrobial Agents and Chemotherapy 44(1), 88-96, 2000, reports that “malaria parasite proliferates by digesting hemoglobin in erythrocytes and oxidizing the hemoglobin to convert it to methemoglobin. Since riboflavin is able to reduce methemoglobin to hemoglobin, the treatment with riboflavin reduced the amount of hemoglobin in the body of malaria parasite, resulting in inhibition of proliferation of malaria parasite.”
However, the medicines for immunostimulation and infection-protection and -treatment, the medicines for preventing or treating sepsis and the medicines for preventing or treating septic shock as mentioned above are not always effective on all patients or animals and the efficacy of these medicines is not also satisfactory. Therefore, the development of medicines for immunostimulation and infection-protection and -treatment, and for preventing or treating sepsis and septic shock with better efficacy is desired.